This proposal seeks funding for the acquisition of a liquid state 400 MHZ (9 4 Tesla) NMR spectrometer to support research in bioorganic chemistry and physical biochemistry at Penn State University The proposed spectrometer will be equipped to perform a variety of state- of-the-art liquid state NMR experiments that are not available on the existing spectrometers at the NMR Facility. The spectrometer will have double resonance (H-X) capability, single axis magnetic field gradient capability, and multinuclear (H-X) selective pulse capability. It will be used to elucidate structure and atomic connectivity along the synthetic pathways of complex natural products and to characterize the proximity and stereospecific binding of biomedically important compounds to a wide variety of organic/inorganic molecules and materials. Much of the structural elucidation will be obtained with double resonance 1H detected NMR experiments such as HMQC, HMBC, and 1H-detected inadequate. Selective pulse methods for the determination of long range 3JCH coupling constants will be used to characterize critical dihedral angles and to optimize HMBC experiments. Magnetic field gradients are necessary for some experiments such as 1H-detected inadequate and long range 3JCH determination, but will also be useful for general 2D and selective pulse experiments where the concentration is sufficient to obtain good Now signals in one or two scans. The proposed spectrometer will be housed and maintained in the Penn State NMR Facility.